Azri S, Renton K W
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Pharmacol Exp Ther. 1987 Dec;243(3):1089-94.
The level of cytochrome P-450 and the oxidation of aminopyrine and benzo(a)pyrene hydroxylase were depressed in hepatic microsomes prepared from mice infected with the gram positive bacteria Listeria monocytogenes. Maximum depression of mixed function oxidase occurred on the 2nd day of infection. This loss in drug biotransformation capacity in the liver was correlated directly with the number of organisms found in that organ. The ability of mice to metabolize drugs in vivo also was impaired during Listeria monocytogenes infection. During the infective period the half-life of theophylline was significantly prolonged and the N-demethylation of aminopyrine as measured by the expiration of 14CO2 from radiolabeled aminopyrine was diminished. The loss of drug metabolism was not due to interferon production, fever or morphological damage to the liver. These results indicate that certain bacterial infections can depress drug biotransformation and elimination in a similar manner to that already reported in viral and parasitic infections. This finding may be of significance to patients receiving drugs which are metabolized by the mixed function oxidase system during episodes of infection with some bacteria.
从感染革兰氏阳性菌单核细胞增生李斯特菌的小鼠制备的肝微粒体中，细胞色素P - 450水平、氨基比林氧化及苯并(a)芘羟化酶活性均降低。混合功能氧化酶在感染第2天出现最大程度的降低。肝脏中药物生物转化能力的这种丧失与该器官中发现的细菌数量直接相关。在单核细胞增生李斯特菌感染期间，小鼠体内药物代谢能力也受损。在感染期，茶碱的半衰期显著延长，通过放射性标记氨基比林呼出14CO2来测定的氨基比林N - 去甲基化减少。药物代谢的丧失并非由于干扰素产生、发热或肝脏形态学损伤。这些结果表明，某些细菌感染可与已报道的病毒和寄生虫感染类似的方式抑制药物生物转化和消除。这一发现对于在感染某些细菌期间接受由混合功能氧化酶系统代谢的药物的患者可能具有重要意义。
